– Microbiome analyses demonstrate engraftment of SER-287-derived bacteria; microbiome compositional changes correlate with clinical remission –
– SER-287 engraftment maintained four weeks after completion of dosing –
– Company to discuss proposed SER-287 development plan with FDA and intends to initiate next clinical trial in mid-2018 –
– FDA granted SER-287 Orphan Drug designation for treatment of pediatric UC patients –
CAMBRIDGE, MA, USA I January 4, 2017 I Seres Therapeutics, Inc., (NASDAQ:MCRB) today announced initial microbiome results from its Phase 1b study of SER-287, a microbiome therapeutic candidate derived from healthy individuals, in patients with mild-to-moderate Ulcerative Colitis (UC) who were failing current therapies. Analyses of study patients’ microbiome data, a co-primary study endpoint of the trial, demonstrate that SER-287 induced dose-dependent engraftment of SER-287-derived bacterial species into the colonic microbiome of the patients treated with SER-287. Patients administered vancomycin pre-treatment followed by daily administration of SER-287 had the highest level of SER-287 engraftment, which was statistically significant. This patient cohort corresponded with the study arm where the most significant clinical benefits were observed, including clinical remission and endoscopic improvement. Differences in the composition of the microbiome post treatment were also associated with clinical remission. Bacterial engraftment signatures were durable throughout the dosing period of the trial and were also observed at four weeks post administration of the final SER-287 dose. The SER-287 Phase 1b study microbiome data support the previously reported clinical results.
“These microbiome data provide Seres with important proprietary insights into the mechanisms of action of SER-287 in Ulcerative Colitis and inform the study design of our next SER-287 clinical trial. The SER-287 bacterial signatures identified in humans also provide indispensable clinical insights towards optimizing the composition of SER-301, a rationally designed microbiome therapeutic candidate for UC and other forms of inflammatory bowel disease,” said Roger J. Pomerantz, M.D., President, CEO and Chairman of Seres. “We look forward to discussing the SER-287 clinical and microbiome data with the FDA as we move this program forward in clinical development.”
SER-287 Phase 1b study design, summary of previously reported clinical results
As reported in October 2017, Seres completed a successful Phase 1b study of SER-287 in patients with mild-to-moderate UC who were failing current therapies. The SER-287 Phase 1b study, a randomized, double-blinded, placebo-controlled, multiple-dose, induction study, enrolled 58 patients with mild-to-moderate UC. Patients were assigned to one of three SER-287 treatment arms or a placebo arm for an eight-week treatment period. SER-287 arms included a daily dosing arm with six days of oral vancomycin pre-treatment, a weekly dosing arm without vancomycin pre-treatment, and a weekly dosing arm with six days of oral vancomycin pre-treatment. Clinical study results demonstrated that SER-287 administration resulted in a dose-dependent improvement of clinical remission rates and endoscopic results. High clinical response placebo rates that were not differentiated from the SER-287 treatment arms were observed. Clinical response is a subjective endpoint and is prone to high variability, as previously observed in several other UC trials of various drug types1. In the most recent FDA regulatory guidance, clinical remission, and not clinical response, is recommended as the primary endpoint in UC registrational studies. The SER-287 Phase 1b safety and tolerability profile observed was very favorable.
Seres used stool samples and whole metagenomic sequencing analyses that enable species-level resolution analyses to characterize changes in the gastrointestinal microbiome.
Microbiome study results
Microbiome results demonstrated engraftment of SER-287-derived bacterial species in patients pre-treated with vancomycin who received SER-287. The degree of SER-287 engraftment, as measured by the number of detectable SER-287-derived bacterial species, increased in a dose-dependent manner, with daily dosing providing the most rapid and robust change in patients’ microbiome. Engraftment was maintained during the entire dosing period and was observed four weeks after the last dose of SER-287 was administered. Thus, engraftment was durable. Changes in the composition of the gastrointestinal microbiome were associated with clinical remission.
Vancomycin pre-treatment, as compared to placebo pre-treatment, led to an immediate reduction of microbiome diversity followed by rapid and robust engraftment of SER-287-derived bacterial species. These data suggest that vancomycin pre-treatment opens ecological niches for SER-287 engraftment in the human microbiome of patients with UC.
Seres intends to present additional study data in a webcast company presentation at the 2018 JP Morgan Healthcare Conference on Thursday, Jan. 11 at 8:30 a.m. PT. A live audio webcast of the presentation will be available under the “Investors and Media” section of Seres’ website. A replay of the presentation will become available approximately one hour after the event and will be archived for 21 days.
About SER-287
SER‐287 is a biologically sourced, oral formulation containing a consortium of live bacterial spores that is being developed for Ulcerative Colitis and other forms of inflammatory bowel disease. The FDA has designated SER-287 as an Orphan Drug for pediatric Ulcerative Colitis. SER-287 is hypothesized to act through a novel mechanism of action by modulating the dysbiotic microbiome, reducing inflammation without immunosuppression effects. A healthy microbiome has been shown to maintain the integrity of the colonic barrier, reduce the signaling by pro-inflammatory molecules produced by certain bacteria, and induce regulatory T cells in the colon to modulate immune responses.2
About Ulcerative Colitis
Ulcerative Colitis (UC) is a serious chronic condition affecting approximately 700,000 individuals in the United States. The disease results in inflammation of the colon and rectum and can cause debilitating symptoms, including abdominal pain, bowel urgency, and diarrhea. Severe cases of UC may result in surgical removal of the colon.
About Seres Therapeutics
Seres Therapeutics, Inc., is a leading microbiome therapeutics platform company developing a novel class of biological drugs that are designed to treat disease by restoring the function of a dysbiotic microbiome, where the natural state of bacterial diversity and function is imbalanced. Seres’ lead program, SER-109, has obtained Breakthrough Therapy and Orphan Drug designations from the U.S. Food and Drug Administration and is in Phase 3 development for multiply recurrent C. difficile infection. Seres’ clinical candidate SER-287 has successfully completed a Phase 1b study in patients with mild-to-moderate Ulcerative Colitis and has obtained Orphan Drug designation in pediatric UC. Seres is also developing SER-262, the first-ever synthetic microbiome therapeutic candidate, in a Phase 1b study in patients with primary C. difficile infection.
References
- Jairath V. et al., Systematic review and meta-analysis: placebo rates in induction and maintenance trials in ulcerative colitis; Journal of Crohn’s and Colitis, 2016
- Blander JM et al., Regulation of inflammation by microbiota interactions with the host, Nature Immunology, 2017; Lynch S and Pedersen O, The Human Intestinal Microbiome in Health and Disease, The New England Journal of Medicine, 2016.
SOURCE: Seres Therapeutics
Post Views: 43
– Microbiome analyses demonstrate engraftment of SER-287-derived bacteria; microbiome compositional changes correlate with clinical remission –
– SER-287 engraftment maintained four weeks after completion of dosing –
– Company to discuss proposed SER-287 development plan with FDA and intends to initiate next clinical trial in mid-2018 –
– FDA granted SER-287 Orphan Drug designation for treatment of pediatric UC patients –
CAMBRIDGE, MA, USA I January 4, 2017 I Seres Therapeutics, Inc., (NASDAQ:MCRB) today announced initial microbiome results from its Phase 1b study of SER-287, a microbiome therapeutic candidate derived from healthy individuals, in patients with mild-to-moderate Ulcerative Colitis (UC) who were failing current therapies. Analyses of study patients’ microbiome data, a co-primary study endpoint of the trial, demonstrate that SER-287 induced dose-dependent engraftment of SER-287-derived bacterial species into the colonic microbiome of the patients treated with SER-287. Patients administered vancomycin pre-treatment followed by daily administration of SER-287 had the highest level of SER-287 engraftment, which was statistically significant. This patient cohort corresponded with the study arm where the most significant clinical benefits were observed, including clinical remission and endoscopic improvement. Differences in the composition of the microbiome post treatment were also associated with clinical remission. Bacterial engraftment signatures were durable throughout the dosing period of the trial and were also observed at four weeks post administration of the final SER-287 dose. The SER-287 Phase 1b study microbiome data support the previously reported clinical results.
“These microbiome data provide Seres with important proprietary insights into the mechanisms of action of SER-287 in Ulcerative Colitis and inform the study design of our next SER-287 clinical trial. The SER-287 bacterial signatures identified in humans also provide indispensable clinical insights towards optimizing the composition of SER-301, a rationally designed microbiome therapeutic candidate for UC and other forms of inflammatory bowel disease,” said Roger J. Pomerantz, M.D., President, CEO and Chairman of Seres. “We look forward to discussing the SER-287 clinical and microbiome data with the FDA as we move this program forward in clinical development.”
SER-287 Phase 1b study design, summary of previously reported clinical results
As reported in October 2017, Seres completed a successful Phase 1b study of SER-287 in patients with mild-to-moderate UC who were failing current therapies. The SER-287 Phase 1b study, a randomized, double-blinded, placebo-controlled, multiple-dose, induction study, enrolled 58 patients with mild-to-moderate UC. Patients were assigned to one of three SER-287 treatment arms or a placebo arm for an eight-week treatment period. SER-287 arms included a daily dosing arm with six days of oral vancomycin pre-treatment, a weekly dosing arm without vancomycin pre-treatment, and a weekly dosing arm with six days of oral vancomycin pre-treatment. Clinical study results demonstrated that SER-287 administration resulted in a dose-dependent improvement of clinical remission rates and endoscopic results. High clinical response placebo rates that were not differentiated from the SER-287 treatment arms were observed. Clinical response is a subjective endpoint and is prone to high variability, as previously observed in several other UC trials of various drug types1. In the most recent FDA regulatory guidance, clinical remission, and not clinical response, is recommended as the primary endpoint in UC registrational studies. The SER-287 Phase 1b safety and tolerability profile observed was very favorable.
Seres used stool samples and whole metagenomic sequencing analyses that enable species-level resolution analyses to characterize changes in the gastrointestinal microbiome.
Microbiome study results
Microbiome results demonstrated engraftment of SER-287-derived bacterial species in patients pre-treated with vancomycin who received SER-287. The degree of SER-287 engraftment, as measured by the number of detectable SER-287-derived bacterial species, increased in a dose-dependent manner, with daily dosing providing the most rapid and robust change in patients’ microbiome. Engraftment was maintained during the entire dosing period and was observed four weeks after the last dose of SER-287 was administered. Thus, engraftment was durable. Changes in the composition of the gastrointestinal microbiome were associated with clinical remission.
Vancomycin pre-treatment, as compared to placebo pre-treatment, led to an immediate reduction of microbiome diversity followed by rapid and robust engraftment of SER-287-derived bacterial species. These data suggest that vancomycin pre-treatment opens ecological niches for SER-287 engraftment in the human microbiome of patients with UC.
Seres intends to present additional study data in a webcast company presentation at the 2018 JP Morgan Healthcare Conference on Thursday, Jan. 11 at 8:30 a.m. PT. A live audio webcast of the presentation will be available under the “Investors and Media” section of Seres’ website. A replay of the presentation will become available approximately one hour after the event and will be archived for 21 days.
About SER-287
SER‐287 is a biologically sourced, oral formulation containing a consortium of live bacterial spores that is being developed for Ulcerative Colitis and other forms of inflammatory bowel disease. The FDA has designated SER-287 as an Orphan Drug for pediatric Ulcerative Colitis. SER-287 is hypothesized to act through a novel mechanism of action by modulating the dysbiotic microbiome, reducing inflammation without immunosuppression effects. A healthy microbiome has been shown to maintain the integrity of the colonic barrier, reduce the signaling by pro-inflammatory molecules produced by certain bacteria, and induce regulatory T cells in the colon to modulate immune responses.2
About Ulcerative Colitis
Ulcerative Colitis (UC) is a serious chronic condition affecting approximately 700,000 individuals in the United States. The disease results in inflammation of the colon and rectum and can cause debilitating symptoms, including abdominal pain, bowel urgency, and diarrhea. Severe cases of UC may result in surgical removal of the colon.
About Seres Therapeutics
Seres Therapeutics, Inc., is a leading microbiome therapeutics platform company developing a novel class of biological drugs that are designed to treat disease by restoring the function of a dysbiotic microbiome, where the natural state of bacterial diversity and function is imbalanced. Seres’ lead program, SER-109, has obtained Breakthrough Therapy and Orphan Drug designations from the U.S. Food and Drug Administration and is in Phase 3 development for multiply recurrent C. difficile infection. Seres’ clinical candidate SER-287 has successfully completed a Phase 1b study in patients with mild-to-moderate Ulcerative Colitis and has obtained Orphan Drug designation in pediatric UC. Seres is also developing SER-262, the first-ever synthetic microbiome therapeutic candidate, in a Phase 1b study in patients with primary C. difficile infection.
References
- Jairath V. et al., Systematic review and meta-analysis: placebo rates in induction and maintenance trials in ulcerative colitis; Journal of Crohn’s and Colitis, 2016
- Blander JM et al., Regulation of inflammation by microbiota interactions with the host, Nature Immunology, 2017; Lynch S and Pedersen O, The Human Intestinal Microbiome in Health and Disease, The New England Journal of Medicine, 2016.
SOURCE: Seres Therapeutics
Post Views: 43
